New method helps identify causal mechanisms in depression.

A new study in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging looks at the driving influence of brain regions in depression.What the researchers say: The researchers note that people with major depressive disorder have alterations in the activity and connectivity of brain systems underlying reward and memory. The findings provide clues as to which regions of the brain could be at the root of depressive symptoms, such as reduced happiness and pleasure.

The research uses a new approach to measure the influence of one brain region on another, referred to as effective connectivity, in depression. The approach goes beyond the limitations of previous brain imaging studies, which show if—but not how—activity of different brain regions is related. “The new method allows the effect of one brain region on another to be measured in depression, in order to discover more about which brain systems make causal contributions to depression,” said the lead researcher.

“This represents an exciting new methodological advance in the development of diagnostic biomarkers and the identification of critical brain circuitry for targeted interventions for major depression,” he added.

The team compared 336 people with major depressive disorder to 350 healthy controls. Brain regions involved in reward and subjective pleasure received less drive (or reduced effective connectivity) in depressed patients, which may contribute to the decreased feeling of happiness in depression.

In addition, brain regions involved in punishment and responses when a reward is not received had decreased effective connectivity and increased activity, providing evidence for the source of sadness that occurs in the disorder.

Memory-related areas of the brain had increased activity and connectivity in people with depression, which the authors suggest may be related to heightened memory processing, possibly of unpleasant memories, in depression.

“These findings are part of a concerted approach to better understand the brain mechanisms related to depression, and thereby to lead to new ways of understanding and treating depression,” said the researchers.

So what? This study, together with the first one reported here, show that there is an increasing interest in the connectivity of the brain in the development of depression—or at least some depression since there are potentially many, many, forms of the disease. Certainly the idea of looking at the connectivity that underlies the experience—or lack of experience—of pleasure or the inability to remember pleasurable things or experiences is novel. If depression really is a collection of diverse symptoms with a zillion possible origins then it makes perfect sense to target the symptomology since the underlying cause—biological or experiential—may be impossible to identify or treat in any individual.